It has been a long, complex year for Leonard Lee Bailey, the surgeon who one year ago shook the world by transplanting a walnut-sized baboon heart to replace the failing heart of an infant who would become celebrated as Baby Fae.
The transplant sustained Baby Fae for only 20 days, and no one was more surprised or more disappointed at the failure than Bailey, a pediatric heart surgeon at Loma Linda University Medical Center in San Bernardino, Calif. ”It was a near-perfect transplant for the first time out, and I really believed that she would celebrate many birthdays with her new heart,” Bailey said in an interview.
The optimism was misplaced, and Bailey and his colleagues, notably immunologist Sandra Nehlsen-Cannarella, have spent much of the last year trying to pin down what went wrong with the animal-to-human transplant, known as a xenograft. That research and the Baby Fae autopsy results were published last week in the Journal of the American Medical Association (JAMA), but the paper is, in Nehlsen-Cannarella`s words, ”a complicated, unclear picture. We still cannot isolate a certain cause of death. The heart was injured by a combination of factors, but it was not rejected in the classical sense.”
”To our colleagues, and especially to the news media, we are making a plea for patience and understanding,” Bailey said. ”We are asking them to throw off dogma and dated thinking and to go with us on this idea a bit to see where it leads. If I see something that convinces me xenografts will not work, I will set the project aside. But this is not what I am seeing. I am very positive about the potential of xenografts to help infants with hypoplastic left heart syndrome (HLHS, stunted or underdeveloped pumping chamber). But the news media are so impatient and so insatiable. I could never be a deadline journalist, rushing for the phone on a story like Baby Fae. I would prefer to be a news commentator, to be able to sit back and sift the information, and make an informed commentary.”
He added, ”We are working on the notion that an ABO mismatch in blood types foiled the graft.”
The mismatch in blood types is a story in itself. For one thing, it is a presumed mismatch because the Loma Linda surgical team does not know the blood type of the donor baboon. Baby Fae had type O blood, which is very common among humans, but the baboon apparently had AB blood. Among humans, blood groups A and O are most common, B is third, and AB is least common. Among baboons, in contrast, group O blood is extremely rare, and B and AB are the most common.
It is very difficult to type baboon blood, Nehlsen-Cannarella explained, because the identifying antigens (substances to which the body reacts by producing antibodies) are expressed very poorly on the surface of the animal`s blood cells.
The lab where Loma Linda obtained its panel of six baboons is in the Southwestern Foundation for Biomedical Research in San Antonio, a facility that does not type baboon blood. Another lab, however, the New York University Laboratory for Experimental Medicine and Surgery in Primates, of Tuxedo, N.Y., does. The test requires one day, and it would have taken one day for the San Antonio lab to send the samples to New York.
”In hindsight,” Nehlsen-Cannarella said, ”we should have had our baboons blood-typed, but I doubt if this would have changed the outcome in Baby Fae`s case. Recent testing found that only 3 of 1,307 common baboons tested had type O blood, and it is highly unlikely that we could have found a type O baboon for Baby Fae, whom we had to rush into surgery within six days of seeing her. Furthermore, our reading of the scientific literature, as quoted in the JAMA paper, indicated that some human transplants have been successful despite crossing the ABO barrier. We did not think that crossing the ABO barrier would be that significant.”
Bailey now believes that the ABO barrier was a ”a tactical error that had catastrophic consequences.” Because this error, however, is potentially avoidable in the future by using the New York lab run by Doctors Wladyslaw W. Socha and Jan Moor-Jankowski, he also believes that ”xenografts are the only practical resource for treating infants with HLHS,” the birth defect that certainly would have killed Baby Fae. The NYU lab now is being besieged by transplant centers considering xenografts. Animal labs now are willing to selectively breed primates, Bailey said, and ”in time–maybe five years–we should be able to have a number of baboons available from all blood types.”
While Bailey blames the presumed ABO mismatch for the graft failure, Nehlsen-Cannarella, director of the Loma Linda Center for Immunology, thinks that the greater problem–and the hurdle to future xenografts–is the antibodies produced by Baby Fae to attack and kill nonhuman tissue.
”If you`re going to be defeated by an ABO mismatch,” Nehlsen-Cannarella said, ”the rejection is usually hyperacute and within the first 24 to 36 hours. It`s true that we drained Baby Fae of all blood, and the rejection could have been delayed by her retransfusion and remanufacturing of antibodies, but not until 20 days. I think that the ABO factor was `very soft` and only part of a complicated picture, but we`ll proceed with our animal studies to learn more.”
At the time of his interview, Bailey was supervising the successful recovery of ”Baby Moses,” who on Nov. 20 at the age of four days received from Bailey a human infant heart as treatment for HLHS.
The surgeon emphasized, ”It required layers and layers of serendipity for us to find a human heart for Baby Moses. In the past 18 months, this is the only human infant heart we`ve found suitable for transplantation, and our luck in this case was incredible. Nationwide, there are anywhere from 300 to 2,000 infants born every year with HLHS, or one to five every day. At Loma Linda, which is a small medical center, we see about one a month.
”A permanent xenograft is the practical thing to do to treat these infants, but I am willing to consider the use of the xenograft as a potential bridge to a human heart transplant, if this makes people more comfortable.”
He added, though, ”To make the bridge work, we`ll have to get the infant out to three to six months with the xenograft. My hunch is that if the xenograft lasts six months, there will be no need to replace it. It would be silly to remove a graft that is functioning normally.”
The Baby Moses story is itself a rare surgical feat, only the third baby- to-baby heart transplant in history. The previous transplants were performed in England in July, 1984, on a 10-day-old girl, and in New York in 1967 on a 2 1/2-week-old boy. The British patient died 26 days later and the U.S. patient less than seven hours after surgery.
David Hinshaw, the director of surgery at Loma Linda and the man who signed Bailey`s medical degree and helped teach him surgery, said pointedly,
”If there had not been a Baby Fae, there would not be a Baby Moses. Because of the publicity over Baby Fae, the family and doctors of the donor for Baby Moses thought of Loma Linda when the infant died.”
Nehlsen-Cannarella added, ”The furor over Baby Fae has stimulated new interest in xenografts, and not just at Loma Linda. In the next year, we`re likely to see pioneering xenograft experiments being performed not only at Loma Linda, but also in Paris; Pittsburgh, with Dr. Tom Starzl`s group; New York, with Dr. Keith Reemtsma`s group; and Texas. Socha and Moor-Jankowski are being besieged with calls from people interested in doing xenografts.”
Baby Fae lives on in more than memory, and even stern critics of the xenograft now see hope for it as an eventual bridge to a human heart donor. In a critique published in JAMA, Doctors Olga Jonason and Mark Hardy conclude,
”What Dr. Bailey has demonstrated, however, in this remarkable experiment with Baby Fae is that orthotopic (in the same position) heart transplantation is technically feasible in the newborn, that even the strong immune response expected in a xenograft can be successfully suppressed with cyclosporine, and that a xenograft might serve as a most suitable short-term support for the circulation of a newborn with fatal congenital heart disease until a human heart donor can be found.”
Bailey, however, continues to believe in the dream–a permanent xenograft –and those who know him best say that he will dare to try again. There likely will be another Baby Fae in 1986, but only after exhaustive animal studies are reviewed by the Loma Linda University Institutional Review Board and only if the chances for success are distinctly improved.
Commenting on the JAMA paper, Nehlsen-Cannarella said, ”I haven`t seen anything that will stop us from doing a second xenograft, but I also haven`t found anything that convinces me we`re right in our assumptions and that we`ll win our gamble. I`m not as committed to xenografts as Len is, but that`s because he sees the dying babies. At this point, I`m still open to the idea. It`s difficult to separate strong desires and wishes from scientific truth, but I want the Baby Fae concept to work and I still think that there is a good chance it can work. But thinking is not proof, and first we have to test our assumptions on animals, and that work is being done right now.”
Nehlsen-Cannarella added: ”From days 5 to 10 after her xenograft, Baby Fae was doing exceptionally well . . . but I was anxious because I was looking for an immune reaction. It came on day 10, when we began to see signs of a classic rejection. Amazingly, we were able to reverse this threat very easily with cyclosporine.
”Every afternoon at 4 or 4:30 we would get together for a conference on Baby Fae. By day 20, or Nov. 15, 1984, we were beginning to see a general failure of her bodily system, including the kidneys, liver and lungs. It happened very suddenly, and she took a terrible turn for the worst. At the end, we were questioning how much more we should do. Should we, for example, give her a kidney transplant, as some later suggested?
”At the end, we all felt like kicking the wall. We felt very empty, very devastated. It was a helpless and impotent feeling because we had no idea what had gone wrong. We were all lost. . . . At autopsy, the heart showed none of the signs of classical rejection. It was not beefy or floppy or swollen. We think that Baby Fae`s death was due to a combination of causes and we are no closer now than we were a year ago to pinpointing a precise cause.”
For his part, Bailey remains above the battle: ”There are very few free- wheeling immunologists, and immunology, while fascinating, is an imperfect science. It takes a bold surgeon to put immunology to the test.
”The immunologists want to get all their ducks in a row before they act, and the surgeon, who must deal with dying babies, does not have that luxury. You can`t alway armchair this debate. There are some very practical considerations that need to be put to the test. The surgeon must act. Baby Fae and Baby Moses have both required technically demanding procedures. Occasionally, I`ve been accused of replacing a heart because I don`t want to do complicated repairs, but that`s not the case. These infants with HLHS are doomed, unless we can find new hearts for them. That`s my vision and my dream.”
If Bailey is a romantic racing ahead of the scientific rubric of the day, it is a phenomenon that his mentor, Hinshaw, can understand:
”His mind-set is such that he has to believe. It is what makes him such a brilliant surgeon. . . . In surgery, Bailey is a man transformed. You can feel the passion–and the compassion.
”I saw the entire (Baby Moses) operation and I gained a renewed sense of how brilliantly Bailey does his surgery. The actual transfer of the heart required maybe an hour, and the mood in the OR, the pathos of the moment, was overpowering. I was struck with how Bailey was not only fussy and meticulous but simultaneously bold and positive and precise. It was artistry. He worked with a towering calm, and the mood was warm and poignant, and yet accomplished with an icy calm.
”And to be able to see the heartbeat of the brain-dead (donor) infant stopped, the heart captured and taken and transferred to Baby Moses, and then to see it quivering as if to say, `I have to beat, let me go, watch me go,`
and to see it start beating again to give life to another baby, well, believe me, it`s one of the greatest highs you`re ever going to have.
”Bailey is a master surgeon, and he has grown enormously in the past year. I don`t know how the value of xenografts will ultimately shake out–and I don`t believe anyone else does, either–but I believe this:
”Dr. Bailey and the team he`s building are on the verge of making some very important contributions.”
